HIV Specific Immunity in Highly Exposed Uninfected Women

说明)： 来自不同国家的通过性接触感染艾滋病毒的高危妇女可能是 由于获得了对病毒的免疫力而免受感染。多项研究表明，艾滋病毒-- 高度暴露、未感染的女性生殖道中的特异性体液免疫反应。我们的假设 高度暴露的血清阴性(ESN)女性生殖道的局部免疫反应 防止感染艾滋病毒。更好地理解这种潜在的保护性抗体反应 可以洞察粘膜免疫在预防艾滋病毒感染中所起的作用，并可能有助于了解 未来与妇女艾滋病毒预防相关的研究。这个项目的目标是描述艾滋病毒的特征- 美国ESN妇女生殖道特异性抗体反应及比较 来自妇女机构间艾滋病毒研究的艾滋病毒感染精英抑制者和进步者 (WIHS)。我们将确定局部生殖器抗体反应在女性中是否具有更广泛的反应性 这些人曾多次经阴道暴露，但仍未感染。初步数据显示，最低 在中国，超过60%的妇女生殖液中存在艾滋病毒抗体浓度 我们的队列中，许多人对不止一种伪型病毒具有反应性。我们将(1)描述本地化 我们的高危、血清阴性女性队列中的生殖道结合和中和抗体，包括 与广谱中和表位结合的中和抗体的特征(2)评估 生殖道抗体的持久性，包括ADCC、ADCVI和交叉ADCC活性，(3) 系统性红斑狼疮患者HIV感染后生殖道抗体的特异性和频度比较 来自WIHS队列的进步者和精英抑制者，以及(4)比较了 来自卢旺达的ESN妇女的生殖道与来自美国的ESN妇女的生殖道。这将是非常重要的 有必要了解生殖器免疫反应的特定组成部分，以防止 艾滋病毒的异性传播。这一知识可以用来开发一种有效和 选择性地刺激女性生殖道对艾滋病毒感染的保护性局部免疫。 相关性(请参阅说明)： 来自多个伴侣的异性接触的暴露的血清阴性妇女(ESN)在 他们的生殖道对抗艾滋病毒。我们将描述他们的反应，并将其与 暴露后感染的。如果这些研究揭示了由这些病毒产生的抗体类型的差异 对于女性来说，它可以帮助我们了解预防艾滋病毒感染所需的抗体类型。

instructions): Women from different countries who are at high-risk of HIV infection through sexual contact may be protected from infection as a result of acquired immunity to the virus. Several studies demonstrate an HIV- specific humoral immune response in the genital tract of highly exposed, uninfected women. Our hypothesis is that the local immune response in the genital tract in highly exposed seronegative (ESN) women confers protection from infection with HIV. A better understanding of this potentially protective antibody response may provide insight into the role mucosal immunity plays in preventing HIV infection and may help inform Future research related to HIV prevention in women. This goal of this project is to characterize the HIV- specific antibody response in the genital tracts of ESN women from the US and to compare their responses to those of HIV infected elite suppressors and progressors from the Women's Interagency HIV Study (WIHS). We will determine whether the local genital antibody response is more broadly reactive in women who have been repeatedly exposed vaginally but remain uninfected. Preliminary data demonstrate that low concentrations of antibody against HIV are present in the genital fluids of more than 60% of the women in our cohort, many with reactivity against more than one pseudotype of virus. We will (1) characterize local genital tract binding and neutralizing antibodies in our cohort of high risk, seronegative women, including characterization of neutralizing antibodies that bind to broadly neutralizing epitopes (2) evaluate the durability of antibodies in the genital tract including ADCC, ADCVI and cross clade ADCC activity, (3) compare the specificity and frequency of antibodies in the genital tract of ESN women with HIV infected progressors and elite suppressors from the WIHS cohort, and (4) compare the humoral immune response in the genital tract of ESN women from Rwanda with those of ESN women from the US. It would be extremely valuable to know the particular components of the genital immune response that protect against heterosexual transmission of HIV. This knowledge could be used to develop a vaccine that effectively and selectively stimulates protective local immunity in the female genital tract against HIV infection. RELEVANCE (See instructions): Exposed seronegative women (ESN) with heterosexual exposure from multiple partners have antibodies in their genital tract against HIV. We will characterize their response and compare it to that of women who were infected following exposure. If these studies reveal differences in the types of antibodies produced by these women, it could help us understand the type of antibody needed for protection against HIV infection.